Analysis of transmitted HIV drug resistance from 2005 to 2015 in Victoria, Australia: a comparison of the old and the new

Background Baseline genotyping is part of standard-of-care treatment. It reveals that transmitted drug resistance (TDR) continues to be important for the management of HIV infection. Attention is typically focused on determining whether resistance to the protease inhibitors (PI) and reverse transcriptase inhibitors (RTI) occurs. However, the increasing use of integrase inhibitors (INIs) raises a concern that TDR to this class of antiretroviral drug may also occur. Methods: PI and RTI drug resistance genotyping was performed on blood samples collected between 2005 and 2015 from 772 treatment-naïve Victorian patients infected with HIV within the previous 12 months. Integrase genotyping was performed on 461 of the 485 patient samples collected between 2010 and 2015. Results: In the period 2005–10, 39 of 343 patients (11.4%) had at least one PI- or RTI-associated mutation, compared with 34 of 429 (7.9%) during the period 2011–15. Compared with 2005–10, during 2011–15 there was a significant decline in the prevalence of the non-nucleoside-associated mutation K103N and the nucleoside-associated mutations at codons M41 and T215. One patient was detected with a major INI resistance mutation, namely G118R. However, this mutation is rare and its effect on susceptibility is unclear. A small number of patients (n = 12) was infected with HIV containing accessory resistance mutations in the integrase gene. Conclusions: The lack of transmitted resistance to INIs is consistent with a low level of resistance to this class of drugs in the treated population. However, continued surveillance in the newly infected population is warranted as the use of INIs increases.

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Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

Current HIV Research ◽

10.2174/1570162x19666211119111740 ◽

2021 ◽

Vol 19 ◽

Author(s):

Rabia Can Sarinoglu ◽

Uluhan Sili ◽

Ufuk Hasdemir ◽

Burak Aksu ◽

Guner Soyletir ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Transcriptase Inhibitor ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Subtype B ◽

Treatment Naïve ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

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PREVALENCE AND STRUCTURE OF HIV-1 DRUG RESISTANCE AMONG TREATMENT NAÏVE PATIENTS SINCE THE INTRODUCTION OF ANTIRETROVIRAL THERAPY IN THE RUSSIAN FEDERATION

HIV Infection and Immunosuppressive Disorders ◽

10.22328/2077-9828-2019-11-2-75-83 ◽

2019 ◽

Vol 11 (2) ◽

pp. 75-83 ◽

Cited By ~ 2

Author(s):

A. A. Kirichenko ◽

D. E. Kireev ◽

A. E. Lopatukhin ◽

A. V. Murzakova ◽

I. A. Lapovok ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Russian Federation ◽

Antiretroviral Drugs ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Treatment Naïve ◽

The Russian Federation ◽

Hiv 1

Aim: to analyze the prevalence, structure of drug resistance and drug resistance mutations in the protease and reverse transcriptase genes of HIV-1 among treatment naïve patients.Materials and methods. We analyzed protease and reverse transcriptase sequences from 1560 treatment naïve HIV-infected patients from all Federal Districts of the Russian Federation with the first positive immune blot during 1998–2017. Sequences were analyzed for the presence of drug resistance mutations and predicted drug resistance to antiretroviral drugs using two algorithms — Stanford HIVDR Database (HIVdb) and the 2009 SDRM list (CPR).Results. The prevalence of drug resistance mutations was 11,1%. More often the prevalence of drug resistance was found for non-nucleoside reverse transcriptase inhibitor drugs (rilpivirine, nevirapine, efavirenz). The prevalence of transmitted drug resistance associated with mutations from the SDRM list was 5,3%, which is classified by the WHO as a moderate level. However, it should be noted that since the large-scale use of antiretroviral drugs in the Russian Federation, there has been a trend towards a gradual increase in the level of the transmitted drug resistance, and in 2016 it has already reached 6,1%.Conclusion. The results demonstrate the need for regular surveillance of the prevalence of HIV drug resistance to antiretroviral drugs among treatment naïve patients in the Russian Federation.

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Frequency of Transmitted Drug Resistance Mutations Among Treatment-Naïve HIV-1-Infected Individuals at a Tertiary Care Centre in South India

Molecular Diagnosis & Therapy ◽

10.1007/s40291-015-0160-5 ◽

2015 ◽

Vol 19 (5) ◽

pp. 273-275 ◽

Cited By ~ 5

Author(s):

Rajesh Kannangai ◽

Shoba David ◽

Vijayanand C. Sundaresan ◽

Jaiprasath Sachithanandham ◽

Monika Mani ◽

...

Keyword(s):

Drug Resistance ◽

South India ◽

Tertiary Care ◽

Transmitted Drug Resistance ◽

Care Centre ◽

Resistance Mutations ◽

Tertiary Care Centre ◽

Drug Resistance Mutations ◽

Treatment Naïve ◽

Hiv 1

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Transmitted Drug Resistance in Treatment-naïve HIV-Infected VCT clients in Taiwan, 2007–2016

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.1065 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S423-S424

Author(s):

Hung-Chin Tsai ◽

I-Tzu Chen ◽

Susan Shin-Jung Lee ◽

Yao-Shen Chen

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Resistance Mutation ◽

Resistance Testing ◽

Transmitted Drug Resistance ◽

Drug Resistance Testing ◽

Subtype B ◽

Treatment Naïve ◽

Hiv 1 ◽

Level Resistance

Abstract Background The transmission of drug-resistant HIV-1 strains might compromise the efficacy of antiretroviral treatment. The aim of this study was to monitor the prevalence of transmitted drug resistance (TDR) in Taiwan, where free highly active antiretroviral therapy (HAART) was provided since 1997. Methods A cohort study on TDR was conducted in antiretroviral therapy -naïve HIV-1 ¡Vinfected voluntary counseling and testing (VCT) clients from 2007 to 2016 in southern Taiwan. Genotypic drug resistance testing to PR/RT (pol gene) were determined by ViroSeqTM system and drug resistance testing to integrase inhibitors (INSTI) was done by in house PCR. Antiretroviral resistance was interpreted using the HIVdb program of the Stanford University HIV Drug Resistance Database. The patients classified as having low-level resistance, intermediate resistance and high-level resistance were defined as having drug resistance. Resistance-associated mutations were defined by the presence of at least one mutation included in the 2017 drug resistance mutation list of the International AIDS Society-USA consensus guidelines. Results A total of 29384 individuals received a free HIV anonymously screening test during 2007 to 2016. The positive rate for HIV-1 infection was 2%. Sequences were obtained from 407 individuals, of whom 90% were infected by MSM, and 10% were infected by heterosexually. Subtype B HIV-1 strains were found in 97%, subtype C in 0.3% and subtype CRF01_AE in 2.7%. A total of 6% was found to harbor drug resistance strains. The most common NRTI resistance associated mutation was D67N, M184V, K219N, Y118I and T215S/P. The most common NNRTI resistance associated mutation was Y181C, K103N, V179D and Y318F. No any one harbored resistance to INSTI inhibitors (n = 188). Conclusion The resistance prevalence (6%) in this study supported the WHO guideline to prescribe pol resistance testing before initiation of HAART therapy in the treatment naïve patients. Disclosures All authors: No reported disclosures.

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Increasing Prevalence of HIV-1 Transmitted Drug Resistance in Portugal: Implications for First Line Treatment Recommendations

Viruses ◽

10.3390/v12111238 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1238

Author(s):

Marta Pingarilho ◽

Victor Pimentel ◽

Isabel Diogo ◽

Sandra Fernandes ◽

Mafalda Miranda ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Resistance Mutation ◽

Drug Resistance Mutation ◽

Transmitted Drug Resistance ◽

Reverse Transcriptase Inhibitors ◽

Genotypic Resistance ◽

Acquired Drug Resistance ◽

Subtype B ◽

Number Of Patients

Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.

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Retrospective Analysis of HBV Pre-Existing Mutations and Drug-induced Resistance Mutations in Patients with Hepatitis B Virus-Related Cirrhosis

Integrative Gastroenterology and Hepatology ◽

10.18314/igh.v2i1.1962 ◽

2019 ◽

pp. 185-192

Author(s):

Wang Liping ◽

Dai Mingjia ◽

Li Chunyang ◽

Hao Jungui ◽

Ji Fang ◽

...

Keyword(s):

Drug Resistance ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Resistance Mutation ◽

Drug Resistant ◽

Resistance Mutations ◽

Drug Induced ◽

B Virus ◽

Treatment Naïve ◽

Mutation Pattern

Background: The reported prevalence and necessity of detection of HBV reverse transcriptase (RT) mutation prior to treatment is varied and remains controversial. This study aimed to identify the prevalence of HBV pre-existing gene resistance mutations and compare the difference between pre-existing mutations and drug-induced resistance mutations in patients with hepatitis B virus-related cirrhosis.Methods: 180 patients with hepatitis B virus-related cirrhosis which included 68 patients with virological breakthrough and 112 treatment-naive cirrhosis patients were retrospectively enrolled. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. One-way ANOVA analysis was performed in the comparison among different groups. Ratios difference was compared with the chi-square test.Results: There were 48 patients (48/112, 42.86%) with drug resistance mutations in nucleoside/nucleotide analogues (NAs) treatment-naive group, 59 patients (59/68, 86.76%) showed drug-resistant mutations in the NAs treatment group. The gene resistance mutation patterns in treatment-naive group were mainly rtS213T, rtV214A, 191V/I and rtN/H238T/D, and the types of resistance mutations in the treated group were different. The adefovir (ADV) group: mainly rtA181T/V and rtS213T; lamivudine/ telbivudine (LAM/LDT) group: rtL180M+ rtM204I/V/S and rtM204I/V/S or a complex mutation pattern containing 204 site; entecavir (ETV) group: The drug resistance pattern is the simultaneous presence of multiple site mutations. LAM/LDT sequential ADV group: The variant type was multi-site and resistant to both ADV and LAM.Conclusion: There was a prevalence of pre-existing mutations in RT region of HBV polymerase in patients with hepatitis B virus-related cirrhosis, The mutation pattern is mainly related to LAM and ADV-related compensatory mutations, while the drug-induced mutation pattern is more complicated, mainly related to the antiviral drugs used and there are mainly primary mutations. Patients with cirrhosis should be tested genetic resistance mutation before using antiviral drugs.

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Increasing prevalence of HIV-1 Transmitted Drug Resistance in Portugal: implications for first line treatment recommendations

10.1101/2020.03.17.20033092 ◽

2020 ◽

Author(s):

Marta Pingarilho ◽

Victor Pimentel ◽

Isabel Diogo ◽

Sandra Fernandes ◽

Mafalda Miranda ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Acquired Drug Resistance ◽

Public Health Programs ◽

Phenotypic Resistance ◽

A Value ◽

Number Of Patients

AbstractBackgroundTreatment for all recommendations has allowed access to antiretroviral (ARV) treatment to an increasing number of patients. This minimizes transmission of infection but can potentiate the risk for development of transmitted drug resistance (TDR) and acquired drug resistance (ADR).ObjectiveTo study the trends of TDR and ADR in patients followed in Portuguese hospitals between 2001 and 2017.Method11911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutations according to the WHO surveillance list. Phenotypic resistance to ARV was evaluated with Standford HIVdb v7.0. Patterns of TDR, ADR and prevalence of mutations over time were analysed with logistic regression.ResultsThe prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (pfor-trend<0.001). This was due to a significant increase of both resistance mutations to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs) from 5.6% to 6.7% (pfor-trend=0.002) and 2.9% to 8.9% (pfor-trend<0.001), respectively. TDR to Protease Inhibitors decreased from 4.0% in 2003 to 2.2 in 2017 (pfor-trend =0.985). Paradoxically, the prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (pfor-trend<0.001) caused by a declining drug resistance to all ARV classes (pfor-trend<0.001).ConclusionsWhile ADR is declining since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgent to develop public health programs to monitor levels and patterns of TDR in newly diagnosed patients.

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Transmitted drug resistance and transmission clusters among HIV-1 treatment-naïve patients in Guangdong, China: a cross-sectional study

Virology Journal ◽

10.1186/s12985-021-01653-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Yun Lan ◽

Linghua Li ◽

Xiang He ◽

Fengyu Hu ◽

Xizi Deng ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Cross Sectional ◽

Genetic Transmission ◽

Treatment Naïve ◽

Hiv 1

Abstract Background Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. Methods The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. Results A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. Conclusions There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

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